The proposed research is aimed towards the definition of organ-specific non-MHC-coded alloantigens of human renal, cardiac and B-lymphocyte tissues. Our preliminary findings for such an antigenic system in human kidneys and their possible role in allograft failure will be expanded to renal, cardiac transplants using eluates prepared from rejected grafts, longitudinal screening of the serum samples, and preparation of both hetero and monoclonal (mouse-mouse and mouse-human heterohybridomas) antibodies defining organ-specific antigens. The target cells will include renal and cardiac biopsy tissues in addition to normal fibroblasts and human mononuclear cell population prepared from peripheral blood. The serological specificities of the antigens and their exact cellular localization will be defined by immunofluorescence, immunoperoxidase and electron microscopic analysis. An attempt will also be made towards cell surface labeling of these antigens followed by immunoprecipitation and characterization on SDS-PAGE. Relationship between organ-specific antigens and MHC-coded alloantigens and their interrelationship in eliciting an immune response against organ-specific antigens will be investigated. In addition, the antigenic determinants defined by the pretransplant B-cell reactive "enhancing" type of antibodies will be identified and immunochemically characterized.